rs13210247

Variant names:

• chr6-111601517-A-G
• rs13210247
• NM_147686.4:c.-9+4259T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147686.4(TRAF3IP2):​c.-9+4259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 274,980 control chromosomes in the GnomAD database, including 1,437 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (979 hom., cov: 32)
  • Exomes 𝑓: 0.078 (458 hom.)
• Consequence: TRAF3IP2 NM_147686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 39 publications found

Genes affected

TRAF3IP2 (HGNC:1343): (TRAF3 interacting protein 2) This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor family. These factors play a central role in innate immunity in response to pathogens, inflammatory signals and stress. This gene product interacts with TRAF proteins (tumor necrosis factor receptor-associated factors) and either I-kappaB kinase or MAP kinase to activate either NF-kappaB or Jun kinase. Several alternative transcripts encoding different isoforms have been identified. Another transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene. [provided by RefSeq, Aug 2009]

ENSG00000255389 (HGNC:):

TRAF3IP2-AS1 (HGNC:40005): (TRAF3IP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147686.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	NM_147686.4	MANE Select	c.-9+4259T>C		intron	N/A	NP_679211.2	O43734-2
	TRAF3IP2	NM_147200.3		c.-92-211T>C		intron	N/A	NP_671733.2	O43734-1
	TRAF3IP2	NM_001164281.3		c.-9+4259T>C		intron	N/A	NP_001157753.1	O43734-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP2	ENST00000368761.11	TSL:1 MANE Select	c.-9+4259T>C		intron	N/A	ENSP00000357750.5	O43734-2
	TRAF3IP2	ENST00000340026.10	TSL:1	c.-92-211T>C		intron	N/A	ENSP00000345984.6	O43734-1
	TRAF3IP2	ENST00000528599.1	TSL:1	n.187+4259T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15496 AN: 152090 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0515

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0777 AC: 9541 AN: 122772 Hom.: 458 Cov.: 0 AF XY: 0.0776 AC XY: 4908 AN XY: 63238

African (AFR) AF: 0.165 AC: 756 AN: 4592

American (AMR) AF: 0.161 AC: 846 AN: 5262

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 519 AN: 4718

East Asian (EAS) AF: 0.0381 AC: 429 AN: 11254

South Asian (SAS) AF: 0.0725 AC: 346 AN: 4772

European-Finnish (FIN) AF: 0.0674 AC: 474 AN: 7030

Middle Eastern (MID) AF: 0.106 AC: 61 AN: 574

European-Non Finnish (NFE) AF: 0.0708 AC: 5437 AN: 76832

Other (OTH) AF: 0.0870 AC: 673 AN: 7738

GnomAD4 genome AF: 0.102 AC: 15524 AN: 152208 Hom.: 979 Cov.: 32 AF XY: 0.101 AC XY: 7482 AN XY: 74426

African (AFR) AF: 0.170 AC: 7065 AN: 41514

American (AMR) AF: 0.140 AC: 2138 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3472

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5190

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4822

European-Finnish (FIN) AF: 0.0599 AC: 635 AN: 10600

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4419 AN: 68010

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.0839 Hom.: 875

Bravo AF: 0.112

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.5
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13210247; hg19: chr6-111922720;